Trunk or branch? Identifying and targeting intratumoral heterogeneity in hepatocellular carcinoma using genomics and patient derived primary cancer cells

Precision oncology aims to deliver personalized treatment to individual patients based on genomic profiling of tumors (1). Molecular targeted therapies have been developed based on the identification of “oncogene drivers” from large-scale genomic studies; leading to several successful genotype-directed clinical applications of targeted therapies (2,3). However, complete and durable responses to these therapies are rare, and the residual tumors eventually acquired new mutations or rewired signaling pathways to by-pass blockade of these targeted therapies (4-6). Moreover, intratumoral heterogeneity (ITH) and tumor evolution play key roles in resistance mechanisms in targeted therapies (7). Therefore, current research efforts have been focusing on identifying these molecular changes in resistant tumors in search for more effective rational combination treatment to overcome resistance mechanisms